Loss of ß-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. ß-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of ß-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and ß-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. RESULTS: The loss of ß-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1ß) factors in condylar cartilage were increased in ß-arrestin2 null mice compared with WT mice. Moreover, the loss of ß-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. CONCLUSION: In conclusion, we demonstrated for the first time that ß-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, ß-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Sustainable treatment of sewage sludge via plasma-electrolytic liquefaction for bio-friendly production of polyurethane foam.

Safe and green disposal or utilization of sewage sludge (SS) has attracted significant attention as SS is increasingly produced worldwide and emerges as an environmental burden if without proper treatment. In this study, efficient and sustainable treatment of SS was achieved using plasma-electrolytic liquefaction (PEL) with alkaline catalysts including sodium hydroxide (NaOH), sodium carbonate (Na2CO3), and sodium acetate (NaAc) and renewable solvents including polyethylene glycol (PEG) 200 and glycerol. Furthermore, the obtained bio-oil with abundant hydroxyl groups could partially replace polyols derived from fossil energy to synthesize bio-based polyurethane foams (BPUFs) for oil adsorption. The results showed that the Na2CO3 catalyst exhibited better performance and yielded bio-oil with a higher heating value (HHV) of 26.26 MJ/kg, very low nitrogen content (0.14%) and metal ions, and a nearly neutral pH of 7.41, under the optimized conditions. Compared with conventional oil bath liquefaction, PEL can significantly improve the liquefaction efficiency, promote the transfer of metal ions in SS to the solid residue (SR), and facilitate the transfer of nitrogen to the gas phase and SR, thereby upgrading the bio-oil to a certain extent. The BPUFs showed excellent oil adsorption capacity, reusability, and desorption and can play an important role in combating oil spills. The PEL method may provide a green avenue for SS valorization and the comprehensive utilization of the obtained products.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

ß-Cyclodextrin covalent organic framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation.

In this work, a new open-tubular capillary electrochromatography (OT-CEC) column was prepared using ß-cyclodextrin covalent organic framework (ß-CD COF) as a stationary phase. Polydopamine was used to assist fabrication of ß-CD COF on an inner wall of a fused-silica capillary. The coating layer on the capillary was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electroosmotic flow (EOF) was also studied to evaluate the variation of the inner wall of immobilized columns. Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by CEC using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The effects of bonding time and concentration of ß-CD COF, the type, concentration and pH of buffer, applied voltage were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of four analytes were resolved within 15 min with resolutions of 1.63-2.62. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75% and 4.24%, respectively. The results reveal that ß-CD COF has great potential as chiral-stationary phases for enantioseparation in CEC.

Distinct clinical phenotypes of primary Sjögren's syndrome differ by onset age: a retrospective study of 742 cases and review of the literature.

OBJECTIVES: To study the clinical characteristics of primary Sjögren's syndrome (pSS) with different onset age, and perform a review of the literature to confirm if the clinical phenotypes are affected by onset age in patients with pSS. METHODS: Data of 742 patients with pSS were retrospectively analysed. Patients were divided into three groups according to onset age: young-onset pSS (YopSS, <35 years), adult-onset pSS (AopSS, ≥35 and ≤65 years), and elderly-onset pSS (EopSS, >65 years). Clinical characteristics were compared among three groups and further multiple comparisons were conducted by Bonferroni adjustment. The Chi-squared test for linear-by-linear association was used to explore variation tendency. RESULTS: This study included 105 (14.2%), 533 (71.8%), and 104 (14.0%) cases of YopSS, AopSS, and EopSS, respectively. YopSS demonstrated lower prevalence of dry mouth, abnormal Schirmer I tests, and interstitial lung disease (ILD), but higher proportions of low C3 and C4 levels, and ANA, anti-SSA, anti-SSB, and rheumatoid factor (RF) positivity than AopSS and EopSS. The proportions of dry mouth (p=0.004), abnormal Schirmer I tests (p=0.002), and ILD (p<0.001) tended to increase with the increase of onset age, while the prevalence of leukopenia (p=0.011), low C3 (p=0.001), low C4 (p=0.001), and ANA (p<0.001), anti-SSA (p<0.001), anti-SSB (p<0.001) and RF (p<0.001) positivity tended to decrease with an increase in onset age. CONCLUSIONS: YopSS demonstrated less dryness and ILD, but more immunologic disorders. ILD prevalence were directly proportional to onset age of pSS; however, leukopenia, hypocomplementaemia, and autoantibody positivity showed opposite trends.

Risk factors for midcourse correction during treatment of first series of aligners with Invisalign.

INTRODUCTION: This study aimed to analyze risk factors for midcourse correction (MC) during the first series of aligners in treatments with Invisalign (Align Technology, Santa Clara, Calif). METHODS: Three hundred and fourteen patients treated with Invisalign were divided into MC and non-midcourse correction groups according to whether they completed the first series of aligners. Differences between these groups were compared with independent sample t tests, chi-square tests, and Wilcoxon rank sum tests. A multivariate logistic regression analysis was performed to identify independent risk factors, including gender, age, extraction treatment, interproximal reduction, correction steps (steps in first series treatment), overbite, overjet, the curve of Spee, Angle classification, and crowding. RESULTS: The percentage of females (86.3%), Angle Class I malocclusion (62.4%), and nonextraction (56.1%) was relatively higher in all 314 patients. More than half of the patients (73.6%) completed the first series of aligners. Differences between the groups in the number of patients with extraction, correction steps, and the curve of Spee were significant (P <0.05). The proportions of MC were 41.3% and 14.8% in extraction and nonextraction patients, respectively. More initially planned correction steps were seen in the MC group (53.4 ± 15.6 steps). Extraction (adjusted odds ratio, 0.375; P = 0.001) and correction steps (adjusted odds ratio, 1.06; P <0.001) were independent risk factors for MC. CONCLUSIONS: Extraction and the number of initially planned correction steps are independent risk factors for MC. In patients with complex dentofacial abnormalities, such as extraction, MC may be needed to achieve predicted changes.

Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4.

CXCR4 dimerization has been widely demonstrated both biologically and structurally. This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N-terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function.

Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo. METHODS: Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool. RESULTS: Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. No specific side effects related to arginine usage were identified. CONCLUSIONS: When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders: A case report and review of literature.

BACKGROUND: The relation between orthodontic treatment and temporomandibular disorders (TMDs) is under debate; the management of TMD during orthodontic treatment has always been a challenge. If TMD symptoms occur during orthodontic treatment, an immediate pause of orthodontic adjustments is recommended; the treatment can resume when the symptoms are managed and stabilized. CASE SUMMARY: This case report presents a patient (26-year-old, female) with angle class I, skeletal class II and TMDs. The treatment was a hybrid of clear aligners, fixed appliances and temporary anchorage devices (TADs). After 3 mo resting and treatment on her TMD, the patient's TMD symptom alleviated, but her anterior occlusion displayed deep overbite. Therefore, the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves. After the levelling, the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion. After careful examination of temporomandibular joints (TMJ) position, the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion. Eventually, the improved facial appearance and relatively stable occlusion were achieved. The 1-year follow-up records showed there was no obvious change in TMJ morphology, and her occlusion was stable. CONCLUSION: TMD screening and monitoring is of great clinical importance in the TMD susceptible patients. Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: a systematic review and meta-analysis.

Objective: To assess the therapeutic efficacy of botulinum toxin type A (BTX-A) for managing myofascial pain related to temporomandibular disorders (TMDs). Methods: This study was conducted according to the PRISMA 2020 statement guidelines. The PubMed, Embase, and Cochrane Library databases were searched. Only randomized controlled trials were included. The primary outcome was a pain score on the visual analog scale, and the secondary outcomes were maximum mouth opening and adverse effects. The Cochrane risk of bias tool was used to assess risk bias. A meta-analysis of studies with the same interventions, controls, assessment methods, and follow-up durations was performed. Results: A total of 519 studies were retrieved, of which 20 randomized controlled trials were included in the qualitative analysis and six were included in the meta-analysis. The results showed that, compared with placebo, BTX-A injection was more effective at relieving myofascial pain, and its effect was similar to that of conventional methods. However, there was no difference in maximum mouth opening between the two groups. After the study assessment with the RoB 2.0 tool, six studies showed a low risk of bias, 13 studies showed some concerns regarding the reported results, and only one study showed a high risk of bias. Adverse effects of BTX-A injection were observed in four studies. Conclusions: In conclusion, BTX-A is effective at relieving pain in TMD patients but does not improve mouth opening. To minimize adverse effects, we recommend a low dose of BTX-A for TMD patients who do not experience complete pain relief from conservative treatments.

Three-dimensional analysis of hard and soft tissue changes in skeletal class II patients with high mandibular plane angle undergoing surgery.

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.

Treatment of severe open bite and mandibular condyle anterior displacement by mini-screws and four second molars extraction: A case report.

BACKGROUND: Temporomandibular joint (TMJ) disorders are closely related to high-angle and skeletal Class II malocclusion. Sometimes pathological changes in the mandibular condyle can cause open bite to occur after growth is complete. CASE SUMMARY: This article is about the treatment of an adult male patient with a severe hyperdivergent skeletal Class II base, an unusual and gradually occurring open bite and an abnormal mandibular condyle anterior displacement. Because the patient refused surgery, four second molars with cavities and root canal therapy were extracted, and four mini-screws were used for intrusion of the posterior teeth. The treatment duration was 22 mo, and after the treatment, the open bite was corrected and the displaced mandibular condyles were seated back to the articular fossa as shown by cone-beam computed tomography (CBCT). Based on the patient's open bite history, the result of clinical examinations and CBCT comparisons, we believe it is possible that the occlusion interference was eliminated after the four second molars were extracted and the posterior teeth were intruded, and the patient's condyle spontaneously returned to its physiologic position. Finally, a normal overbite was established, and stable occlusion was achieved. CONCLUSION: This case report suggested that identifying the cause of open bite is essential, and the TMJ factors for hyperdivergent skeletal Class II cases should be particularly examined. For these cases, intruding posterior teeth may place the condyle in a more appropriate position and provide an environment suitable for TMJ recovery.

Receptor-interacting protein 1 inhibition prevents mechanical stress-induced temporomandibular joint osteoarthritis by regulating apoptosis and later-stage necroptosis of chondrocytes.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative joint disease that has multiple causes. The abnormal stress distribution is known to be an important trigger of TMJ OA. This article explored the pathological changes of the condylar cartilage under 60 g mechanical force and whether the inhibition of Receptor-interacting protein 1 (RIP1) can protect stress-induced TMJ OA. MATERIAL AND METHODS: We used a compressive mechanical force-induced-TMJ OA model and Lenti-virus targeting RIP1 to perform this study. A total of 72 male rats were used in the animal experiment. Each rat was injected with a negative control Lenti-shRNA in the right TMJ and Lenti-siRIP1 in the left TMJ and euthanized after 4 and 7 days, respectively. Quantitative real-time PCR, immunohistochemistry, Tunnel staining and Micro-CT were used to detect cartilage pathological changes and one way ANOVA with LSD analysis was used to determine statistical significance between groups. RESULTS: The results identified the characteristics of the spatio-temporal changes in stress-induced TMJ OA. Under mechanical force, inflammation and apoptosis, which occur in the whole layer of mandibular cartilage, appear on the 4th day and persist till the 7th day. Necroptosis arises in the later stage of mechanical force and is mainly located in the transition layer. RIP1 inhibition through Lenti-virus could protect stress-induced mandibular cartilage thinning by inhibiting persisted apoptosis and later-stage necroptosis in the transition layer. CONCLUSIONS: RIP1 plays an essential role in the destruction of mandibular cartilage under mechanical force. RIP1 inhibition through Lenti-virus could protect mechanical stress-induced TMJ OA.

Orthodontic-surgical treatment of an Angle Class II malocclusion patient with mandibular hypoplasia and missing maxillary first molars: A case report.

BACKGROUND: Adult patients presenting with Angle Class II division 1 malocclusions that have a strong skeletal etiology can be challenging for clinicians, particularly if accompanied by retrognathia of the mandible and a dolichofacial growth pattern. CASE SUMMARY: In this case report, we describe the successful orthodontic and surgical management of a 20-year-old woman with an Angle Class II malocclusion with a severe anteroposterior skeletal discrepancy characterized by mandibular deficiency. She had incompetent lips, dental and skeletal Class II malocclusion, high mandibular plane angle, mild mandibular crowding, and two missing maxillary first molars. The treatment plan comprised: (1) Extraction of two mandibular second premolars to decompensate and retract mandibular incisors; (2) pre-surgical alignment, leveling, and space closure of the teeth in both arches, and protraction of the second maxillary molars to close the maxillary space; (3) surgical treatment including a LeFort I osteotomy for maxillary retraction and rotation, a bilateral sagittal split osteotomy for mandibular advancement and rotation, and a genioplasty for correctting the skeletal deformities; and (4) post-surgical correction of the malocclusion. CONCLUSION: The patient's facial esthetics was significantly improved and a desirable occlusion was achieved after 16 mo treatment. Follow-up records after 2 years showed stable esthetics and function.

BRD4 inhibition alleviates mechanical stress-induced TMJ OA-like pathological changes and attenuates TREM1-mediated inflammatory response.

The aim of this paper was to investigate the protective effects of bromodomain containing 4 (BRD4) inhibition on the temporomandibular joint osteoarthritis (TMJ OA) induced by compressive mechanical stress and to explore the underlying mechanism. In vivo, a rat model of TMJ compressive loading device was used and BRD4 inhibitor was injected into the TMJ region. HE staining and micro-CT analysis were used for histological and radiographic assessment. Immunohistochemistry and qPCR were performed to detect inflammatory cytokines expressions. High-throughput ChIP-sequencing screening was performed to compare the BRD4 and H3K27ac binding patterns between condylar cartilage from control and mechanical force groups. In vitro, the mandibular condylar chondrocytes were treated with IL-1ß. Small Interference RNA (siRNA) infection was used to silencing BRD4 or TREM1. qPCR was performed to detect inflammatory cytokines expressions. Our study showed that BRD4 inhibition can alleviate the thinning of condylar cartilage and subchondral bone resorption, as well as decrease the inflammatory factors expression both in vivo and in vitro. ChIP-seq analysis showed that BRD4 was more enriched in the promoter region of genes related to the stress and inflammatory pathways under mechanical stress in vivo. Trem1, a pro-inflammatory gene, was screened out from the overlapped BRD4 and H3K27ac increased binding sites, and Trem1 mRNA was found to be regulated by BRD4 inhibition both in vivo and in vitro. TREM1 inhibition reduced the expression of inflammatory factors induced by IL-1ß in vitro. In summary, we concluded that BRD4 inhibition can protect TMJ OA-like pathological changes induced by mechanical stress and attenuate TREM1-mediated inflammatory response.

LOXL2 attenuates osteoarthritis through inactivating Integrin/FAK signaling.

Temporomandibular joint OA (TMJOA) is a common degenerative joint disease, leads to structural damage and ultimately loss of function. Matrix degradation is one of the first pathogenesis during the progression of OA, it was effective to inhibit matrix degradation to block the development of OA. In this study, an in vivo model (compressive mechanical force) and an in vitro model (IL-1ß) were used to induce OA-like changes in TMJ cartilage and chondrocytes. We revealed lysyl oxidase like-2 (LOXL2) play a critical role in TMJOA. LOXL2 expression decreased in mechanical stress/IL-ß induced TMJOA-like lesions in both in vivo models and in vitro models. Furthermore, recombinant LOXL2 (rhLOXL2) treatment ameliorated the degenerative changes induced by mechanical stress in vivo, including the thinning cartilage, down-expression of collagen II and proteoglycan, and over-expression of TNF-a, while LOXL2 antibody (anti-LOXL2) treatment exacerbated these changes. Mechanistically, the protection of LOXL2 in chondrocytes was induced partly through activation of the Integrin/FAK pathway. The inhibition of the Integrin/FAK pathway could neutralized the effects caused by rhLOXL2. Collectively, our study suggests that the LOXL2 plays a protective role in mechanical stress induced TMJOA-like changes, and the Integrin/FAK pathway may be a key downstream pathway in this process.

Controlling the Poly(ε-caprolactone) Degradation to Maintain the Stemness and Function of Adipose-Derived Mesenchymal Stem Cells in Vascular Regeneration Application.

Biodegradable poly(ε-caprolactone) (PCL) scaffolds with adipose-derived mesenchymal stem cells (ADSCs) have been used in vascular regeneration studies. An evaluation method of the effect of PCL degradation products (DP) on the viability, stemness, and differentiation capacities of ADSCs is established. ADSCs are cultured in medium containing different concentrations of PCL DP before evaluating the effect of PCL DP on the cell apoptosis and proliferation, cell surface antigens, adipogenic and osteogenic differentiation capacities, and capacities to differentiate into endothelial cells and smooth muscle cells. The results demonstrate that PCL DP exceed 0.05 mg mL-1 may change the stemness and differentiation capacities of ADSCs. Therefore, to control the proper concentration of PCL DP is essential for ADSCs in vascular regeneration application.

Graphene enhanced transformation of lignin in laccase-ABTS system by accelerating electron transfer.

The degradation of lignin has attracted much attention since it represents approximately 30% of all non-fossil carbon sources and constitutes a sustainable bio-resource for fuels and aromatic derivatives. Here we investigated the degradation of lignin by laccase-catalysed reactions using 2,2'-Azino-bis(3-ethybenzothiazoline-6-sulfonic acid) (ABTS) as a mediator coupled with the carbon material graphene. Results indicated that there was a significant, two-fold, increase in the catalytic activity of lignin degradation in laccase-ABTS systems in the presence of graphene. Analysis suggested that the enhancement of lignin degradation could be attributed to graphene acting as an electron transfer conductor, thereby accelerating electron transfer, which facilitated the formation of intermediate oxidation states of ABTS and rendered the reactions between lignin and ABTS intermediates more efficient. This study could promote the development of novel enzymatic lignin degradation systems coupled with the carbon-based material graphene.

Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress.

OBJECTIVE: To examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS). METHODS: We used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague-Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5Hz, 24h vs 20%, 0.5Hz, 24h) on chondrocytes. For hypoxia experiment, the concentration of O2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method. RESULTS: Tunicamycin, 20% mechanical forces and hypoxia (1% O2) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers. CONCLUSION: We confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation.